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It has previously been shown that rats do not expel a primary infection of Nippostronglus brasiliensis during lactation. In the present paper, three aspects of the immune response of the lactating rat to the parasite were examined and compared with the response of non-lactating rats. Protective and reaginic antibodies were present in the circulation of rats first infected during lactation, in titres as high or higher than those in non-lactating controls. The intestinal mast cell response was similar both in timing and magnitude and lactating rats became susceptible to shock with the i.v. injection of antigen. Attention was drawn to the similarity between the response of the lactating rat and that of the neonate to this infection. [ABSTRACT FROM AUTHOR]

In the previous paper we showed that the immune response to sheep red cells (SRBC) was degenerate; serum antibodies showed increasing loss of specificity, signalled by cross-reactions with horse RBC (HRBC), with time after immunization and with hyperimmunization. In the present report we have analysed the role T cells may play in this process. To do this we studied the antibodies made by mice deprived of T cells by irradiation as well as those made by normal mice immunized with SRBC in distilled water, which was shown to depress the DNA synthetic response of T cells. In both instances the mice with fewer responding T cells made less antibody which could agglutinate HRBC than did the appropriate controls. This was true even when no difference in anti-SRBC titre was apparent. In addition we showed that the antibody made by mice with reduced numbers of T cells was less effective at passive suppression of the immune response to SRBC than was similarly titred (against SRBC) antibody made by normal mice. Thus, certain sub-populations of antibodies, normally made in response to SRBC, immunization, are particularly thymus dependent. We have discussed why we think they are those of particularly high affinity. [ABSTRACT FROM AUTHOR]

Red cells sensitized with naturally occurring or 'immune' fowl antibody were lysed by fresh fowl serum. This fowl complement could not be replaced by that of human, rabbit or guinea pig. Both naturally occurring and 'immune' antibodies to red cells in the mammalian species tested did not lyse with fowl complement. Lysis by fresh fowl serum of sheep red cells sensitized with mammalian antibody is due to the presence of naturally occurrent antibody to these cells in the fowl serum; the enhancement of this lysis by the mammalian antibody will be described more fully in the next paper. Naturally occurring antibody to sheep red cells present in turkey serum and 'immune' antibody to fowl red cells were not lytic with fresh turkey serum, with fowl complement, with guinea-pig complement or with any combination of these. Some properties of fowl complement are given. [ABSTRACT FROM AUTHOR]

The experiments described in this paper extend the observations of previous work in vitro demonstrating a decrease in the frequency of antigenreactive units specific for horse RBC in spleen cells from mice primed with KLH. It was observed that the addition of lymphoid cells having T-cell function reconstituted the anti-HRBC response to normal values. Significant enhancement of the response beyond the normal values could be evoked using two dissimilar methods, (i) addition of allogeneic thymus cells, and (ii) restimulation in vitro with the priming antigen. The latter type enhancement was elicited by the addition of small doses of KLH to cultures of spleen cells from mice recently primed with KLH, including cultures otherwise demonstrating antigen-induced suppression. The stimulus required to enhance the response to HRBC in these cultures was specific for the priming antigen, KLH. These results are discussed in the light of current theories of 'antigenic competition' and specific heterologous enhancement. [ABSTRACT FROM AUTHOR]

This paper describes a method for simultaneous measurement of the accumulation of plasma protein and erythrocytes in skin reactions of hypersensitivity to bovine γ-globulin (BGG) and tuberculin PPD in the guinea-pig. The procedure consists in giving 125I-labelled plasma albumin and 51Cr-labelled autologous erythrocytes together by intravenous injection into guinea-pigs bearing skin lesions of allergic inflammation at different times and for different periods during the development of the skin reactions. Isotope accumulation in excised skin reactions is measured by scintillation counting at different stages during the evolution of hypersensitivity responses. Skin reactions of combined anaphylactic and Arthus hypersensitivity to BGG were characterized by pronounced increased vascular permeability principally in the first hour. In established 24-hour hypersensitivity reactions to both antigens (BGG and PPD) there was continuing accumulation of both plasma albumin and erythrocytes. During the development of the tuberculin reaction, an intermediate phase of isotope accumulation occurred between 6 and 9 hours after skin testing; serum transfer studies showed that this intermediate peak was not attributable to circulating antibody alone. These isotope tracer techniques were also applied to study vascular permeability in systemically transferred reactions of delayed hypersensitivity and in the vascular response to the intradermal injection of an inflammatory factor generated by antigen-activation of sensitized lymphocytes. It was concluded that isotope tracing provided objective and sensitive methods for analyzing microvascular responses in allergic inflammation. [ABSTRACT FROM AUTHOR]

Although induced immunological tolerance of histocompatibility antigens is generally considered to be specific, cases of concomitant third-party unresponsiveness may occur. The present paper describes one case in point. Antigenic overlap between original and third-party donor, as well as runt disease have been excluded as possible explanations for the observed lack of specificity. It is hypothesized that an innate inability, of the host to respond to the relevant third-party antigen(s), or the ability of certain antigens to induce tolerance of themselves as well as of distinct but related antigens, may be responsible for the phenomenon. [ABSTRACT FROM AUTHOR]

This paper describes the course of infection and certain pathological changes in thymus-deprived and normal CBA mice after oral infection with Trichinella spiralis. Greater morbidity was found among deprived mice and deaths due to trichiniasis occurred solely in this group. The local inflammatory response in the gut and skeletal muscles was defective in deprived animals: compared to normal mice it was slower to develop, contained fewer cells and was inadequately sustained. There was a striking paucity of tissue eosinophils and this was correlated with failure of deprived mice to develop a blood eosinophilia. The parasites appeared to persist longer in the gut of deprived animals and progressively more parasites were recovered from the carcasses of these mice at later stages of the infection. The present findings indicate that thymus-dependent cell populations are implicated in the host response to T. spiralis; and some possible modes of action of T cells are discussed. [ABSTRACT FROM AUTHOR]

Rabbits made immunologically unresponsive by neonatal administration of HSA, HGG or BSA were given a course of intravenous injections of the respective antigens, adsorbed on alum, after a lapse of 13-27 months since the last administration of antigen. 8/12 responded to HSA, 4/5 to HGG, 9/10 to BSA, as judged by immune elimination of antigen, but this was delayed in onset and slow compared with that in previously untreated rabbits. The antibody formed was small in quantity and usually failed to precipitate with antigen. The sedimentation coefficients of 131I-labelled antigens, in the presence of excess antibody, were measured by ultracentrifugation through a sucrose density gradient. These showed that only small complexes were formed in some of the non-precipitating antisera. In one instance the diffusion coefficient of the complex was also measured, by a technique based on diffusion through agar gel. The calculated molecular weight of the complex, 330,000 indicated the presence of only two combining sites on the antigen. Combination of the anti-HSA sera with an HSA fragment was also measured. Whereas the amount of the fragment bound by ordinary hyperimmune anti-HSA sera was about one-fifth the HSA bound, the amounts bound by the test sera were relatively much less. Some non-precipitating sera failed to bind the fragment, although they bound HSA. These findings indicate that following neonatally induced immunological unresponsiveness the capacity to respond to antigen returns piecemeal in respect of different parts of the antigenic mosaic, and that it may be severely restricted. The theoretical implications are discussed. [ABSTRACT FROM AUTHOR]

The immunological responses of rabbits to HSA, HGG or BSA were tested at various times later in animals which had received the corresponding antigens before or shortly after birth. As judged by the criterion of failure to show immune elimination of antigen, a high proportion of the rabbits remained unresponsive at times when it was calculated that all the originally administered antigen would have been eliminated from the circulation. Furthermore, removal of antigen by passively administered antibody failed to restore the capacity to respond. It is concluded that, in respect of the antigens used, their persistence in the extracellular body fluids is not a prerequisite for maintenance of immunological unresponsiveness.
Further administration of the same antigen to rabbits which had escaped from a state of specific immunological unresponsiveness generally produced a very weak response, and in a few instances resulted in a return to the unresponsive state.
When the cross-reacting antigens HSA and BSA were administered adsorbed on alum to rabbits made unresponsive by neonatal contact with BSA and HSA respectively, and at the same time a further dose of the original antigen was given, antibodies were formed which were specific for the second antigen and did not cross-react with the first. In only 1/9 animals was responsiveness to the first antigen restored. The significance of these results is discussed. [ABSTRACT FROM AUTHOR]

A state of immunological paralysis has been induced in adult CBA mice by intrapertioneal injections of small quantities of bovine γ globulin (BGG). The minimum paralyzing dose of BGG has been found to be between 50 and 200 μg. A dose as small as 2 μg, has been found to have a slight paralyzing effect. The time necessary for the induction of paralysis by 50 μg to 2 mg of BGG in CBA mice is 3-4 days. Paralysis is induced by only one component of BGG; this component is incapable of inducing an antibody response unless an injection of adjuvant is made at the same time or slightly before the injection of the antigen. The BGG is centrifuged at an RCF of 20,00-30,000 g to remove particulate matter. Failure to remove the particulate matter leads to sporadic immune responses in groups of mice injected with the protein. Mice given a paralyzing injection of BGG were subsequently challenged by an injection of BGG in Freund's adjuvant. The result of this challenge was tested by an injection of radioactively-labelled antigen and the elimination of this antigen from the circulation of the challenged mice was followed for several days. 'Immune elimination' can easily be distinguished from 'non-immune elimination'. The presence of antibody to the non-paralysing components of BGG in sera from paralysed mice was confirmed using the Ouchterlony gel-diffusion technique. [ABSTRACT FROM AUTHOR]

A state of immunological unresponsiveness to bovine serum albumin (BSA) or human gamma globulin (HGG) can be produced in guinea pigs by contact with these proteins either before and soon after birth, or even soon after birth alone. As judged by failure of treated animals to show immune elimination of the antigen, or anaphylaxis on reinjection, the animals were completely unresponsive when tested up to 5 months after birth. Administration of 6-mercaptopurine to guinea pigs, even in lethal doses, did not prevent the development of antibodies to HGG. After administration of BSA or HGG, labelled with 131I, to pregnant guinea pigs, their offspring at term contained significant amounts of the labelled proteins. HGG was catabolized in new-born guinea pigs with the same half-life as in adults. [ABSTRACT FROM AUTHOR]

Cold agglutinins were separated from the sera of eleven patients suffering from the cold-antibody type of acquired haemolytic anaemia by the dissociation of the specific antigen-antibody complexes. The electrophoretic mobility of the cold antibody was found to correspond to that of γl globulin in each case. Ultracentrifugal studies carried out on eluted cold antibodies prepared from the sera of seven patients demonstrated that the antibodies were macromolecules (S20,w∼18.1). In one instance the sedimentation coefficient of the cold antibody was demonstrated to be similar to that of electrophoretically separated ‘γ1 globulin’ prepared from the same serum, indicating their identical physical state. The results of treating the sera of nineteen patients with the cold-antibody type of acquired haemolytic anaemia with mercapto-ethanol further confirmed that the cold antibodies were all macromolecules, whether derived from idiopathic cases or cases secondary to some other known disorder. [ABSTRACT FROM AUTHOR]

Rabbit spleen cells, which have been treated in vitro with certain rabbit or guinea-pig antisera (e.g. against human serum albumin) and washed, are capable of specifically adsorbing radio-isotope labelled antigen. The antibody responsible for this effect appears to be distinct from the main precipitating anti-body in the serum and the term ‘cytophilic antibody’ has been suggested. The activity of the cytophilic antibody is not destroyed by heating at 56° C. for half an hour. The cytophilic antibody is not adsorbed by red cells. Spleen cells which have been treated with methanol before treatment with antiserum take up less antigen than non-methanol-treated cells tested in the same way. However, the addition of flesh normal spleen cells to the methanol-antibody-treated cells before the addition of antigen increased the uptake of the latter. [ABSTRACT FROM AUTHOR]

Cold antibodies were separated from the sera of six patients suffering from the cold-haemagglutinin syndrome and from one patient with acquired haemolytic anaemia secondayr to lymphosarcoma by dissociation of the specific antigen-antibody complexes. The eluted antibodies were studied (a) by immuno-electrophoresis along with the parent sera against horse anti-human serum and (b) by double diffusion in agar gel along with electrophoretically separated ‘γ1 globulin’† against anti-19S ‘γ-globulin’ rabbit sera. The protein forming the cold antibody was localized in the β2-M position on immuno-electrophoresis in each instance. It was found by double diffusion in agar gel to be immunologically identical with the protein forming the abnormal ‘γl-globulin’ electrophoretic peak in the parent serum. The results of these experiments indicate that the cold antibodies derived from patients with the cold-antibody type of acquired haemolytic anaemia are macro-molecular globulins. [ABSTRACT FROM AUTHOR]

A critical review is given of Goldberg's (1952, 1953) theory of Antigen-Antibody reactions in vitro. Goldberg's assumptions and the mathematical development of his theory are described in detail. Comparisons of Goldberg's predictions with experimental results are given in graphical form. Some criticisms are made of Goldberg's use of equations in regions in which the derivations given by him are not valid. [ABSTRACT FROM AUTHOR]

The effect of a single batch of horse anti-mouse thymocyte globulin on the immune response to type III polysaccharide antigen bas been investigated in 2–3-month-old male A/HeJ, C57BI, BALB/c, DBA/I, CBA and C3H mice. In almost all cases the intraperitoneal administration of 5 mg of this material on days -4 and -2 significantly suppressed the immune response to 0·1, 1·0 and 5·0 μg of antigen injected i.v. on day 0. Further studies undertaken in BALB/c mice indicated that effective suppression of the immune response to type III polysaccharide antigen could also be achieved by injecting 5 mg of this product (i.p.) some 15–30 minutes prior to antigenic challenge. Preliminary cell re constitution studies in antilymphocytic antibody-treated CBA mice indicate that the ability to respond to type III polysaccharide can be partially restored by the injection of syngeneic thymocytes, bone marrow cells or spleen cells. [ABSTRACT FROM AUTHOR]

The effect of an horse anti-mouse thymocyte globulin (ALG) preparation on the primary and secondary immune responses to sheep erythrocytes (RBC) was studied in 2-3-month-old male A/HeJ, C57B1, BALB/c, DBA/1, CBA and C3H mice. A wide variation in the primary and secondary responses of the individual strains was noticed but in ail cases these were significantly suppressed by ALG pretreatment. The capacity of the ALG to suppress the primary immune response was not overcome by increasing the antigen dose from 3 × 107 to 3 × 109 sheep RBC. [ABSTRACT FROM AUTHOR]

Bone marrow cells and thymus cells were observed in cell transfer expehments to collaborate in the production of anti-BSA antibodies. The target cells for tolerance induction either with a 'low dose' of antigen (100 µg of deaggregated BSA once a week × 5) or with a 'high dose' (a single injection of 5000 µg) were identified by the same technique. In 'low dose' tolerance, some indication was obtained that thymus-derived cells in peripheral lymphoid systems were the target cells; bone marrow-derived cells appeared not to be so susceptible, and the cells residing in thymus or bone marrow seemed to remain unimpaired, in contrast, the injection of a 'high dose' of tolerogen rendered both types of cells in spleen, thymus cells and bone marrow cells, unresponsive or hyporesponsive in parallel with one another. [ABSTRACT FROM AUTHOR]

Irradiated (NZB × BALB/c)F1 mice were injected with syngeneic bone marrow cells, syngeneic or parental thymus cells, and sheep red cells. The antibody plaque-forming cell response depended on the number of sheep cells and the age and strain of the thymus cells. Young or adult BALB/c thymus, and young hybrid thymus, responded best to low numbers of sheep cells; with higher numbers they became tolerant. Adult hybrid thymus, and young or adult NZB thymus, responded better to high numbers of sheep cells. Hybrid mice irradiated and restored with BALB/c bone marrow developed thymus cells with the reactivity of BALB/c thymus. It is argued that NZB mice, and older hybrids, may develop autoimmunity because of an abnormality of tolerance induction manifested in their thymus cells, but of bone marrow origin. [ABSTRACT FROM AUTHOR]

A complete evaluation of the immunogenicity of oligo-L-lysines and their mono-ε-DNP derivatives requires a determination of their capacity to prepare animals for secondary responses to a highly immunogenic analogue and to elicit secondary responses in animals prepared with such an analogue. It is shown here that 1-ε-DNP-tetra-L-lysine is not effective, or only marginally effective, in preparing PLL+ guinea-pigs for secondary anti-DNP responses to DNP-poly-L-lysine whereas 1-ε-DNP-nona-L-lysine is active in such preparation. Similarly, in animals primed to DNP-ovalbumin, supplemental immunization with tetra-L-lysine is not effective in preparing strain 2 guinea-pigs for a secondary anti-DNP response to DNP-poly-L-lysine whereas both nona-L-lysine and poly-L-lysine are effective, the latter to a considerably greater degree. In animals primed with DNP-poly-Llysine or with DNP-ovalbumin and poly-L-lysine, DNP-poly-L-lysine elicits secondary anti-DNP responses whereas neither 1-ε-DNP-nona-L-lysine or 1-εDNP-tetra-L-lysine do. The data indicate that a hierarchy in the degree of immunogenicity exists within the lysyl peptides series with poly-L-lysine more immunogenic than nona-L-lysine and this, in turn, more immunogenic than tetra-L-lysine which is either nonimmunogenic or marginally immunogenic. Further, the determination of immunogenicity is a feature either of the 'helper' cell population or of a step in the response which is prior to the activation of 'helper' cells. [ABSTRACT FROM AUTHOR]

The onset of the exponential expulsion of Nippostrongylus brasiliensis worms in the rat is associated with a sharp burst of intestinal mast cell activity and increased permeability of the bowel wall. It was found that the onset of maximum velocity of worm expulsion occurred earlier in female rats than in male rats and proceeded at a faster rate. There was a corresponding difference in the timing of the mast cell rise and macromolecular leak between the sexes. This suggested that there is a relationship between these events. Cortisone, a drug known to stop worm expulsion and to suppress the mast cell response, also prevented the macromolecular leak. Electron microscopy showed that during the period of increased permeability a pathway for protein tracers had opened up between the epithelial cells and it is suggested that this is the route for enhanced antibody transfer across mucous membranes. We suggest that a stimulus or stimuli from the parasite cause synchronous development of new populations of mast cells, IgE-producing plasma cells and plasma cells synthesizing antibodies of other classes possessing an anti-worm effect. It is also suggested that these mast cells discharge their pharmacological mediators by an allergen-reaginic antibody mediated system and that these mediators create a pathway through the intestinal mucosa for the translocation of antibody. [ABSTRACT FROM AUTHOR]

The immune response elicited by immunogenic forms of bovine γ-globulin (BGG), such as heat aggregated BGG (aBGG), BGG in Freund's incomplete adjuvant (FIA) or BGG plus endotoxin (ET), was interrupted by a single injection of cyclophosphamide. The amount of soluble BGG (sBGG) required to induce paralysis did not differ significantly between cyclophosphamide-treated mice and untreated mice. The injection of l mh sBGG together with 100 μg aBGG or 10 μg ET caused an immune response in normal mice but induced paralysis in cyclophosphamide-treated mice. However, without sBGG, the administration of aBGG suspension or aBGG in FIA could not induce paralysis, even with the aid of cyclophosphamide. [ABSTRACT FROM AUTHOR]

The enhancement effect of some antigens on in vitro colony formation by normal mouse bone marrow cells is mediated through a normal serum αmacroglobulin (αM) which is present in newborn animals and shows no immunological specificity. The proportion of antigen and αM affects colony enhancement, and it has also been shown that specific antibody successfully competes with αM for the antigen. It seems likely that antigen-αM complex acts directly on the colony forming cell, rather than indirectly through release of colony stimulating factor. The possible relevance of this phenomenon to immune induction and, to the effect of antigens in promoting irradiation survival is discussed. [ABSTRACT FROM AUTHOR]

The immunological response of the primitive mammal Tachyglossus aculeatus has been studied. We have shown that this animal responds to flagella from Salmonella adelaide with production of mercaptoethanol-resistant antibodies during both primary and secondary responses. Although an anamnestic secondary response could be demonstrated, it was of much smaller magnitude than that of phylogenetically higher placental mammals. Serological investigations demon- strated the presence of a mercaptoethanol-sensitive antibody of high molecular weight and an antibody of lower molecular weight which was mercaptoethanol resistant. These two antibodies seem to be analogous to IgM and IgG antibodies of higher mammals. [ABSTRACT FROM AUTHOR]

A number of serum protein fractions were tested for their ability to suppress the immune response of rats injected with washed sheep cells. Significant depression of the immune response was produced by human serum proteins, and by bovine α-globulin fractions. The mechanism of this effect is at present not clear.

The article reports on the effects of the physical state of the antigen and of lymphoreticular cell proliferation on the response to intraperitoneal injection of bovine serum albumin in rabbits. A study was conducted to determine whether the time relationships of Corynebacterium parvum administration and antigen injection are important in particular to show whether it would produce same adjuvant effects as Corynebacterium parvum injected 6 days prior to the injection of the antigen. The result of the study reveals that higher affinity antibody especially if the quantity of antigen available causes specific lymphoid proliferation.

The following three results emerged from the present experiments concerning the induction of antibody synthesis against sulfanilic acid: 1) the anti-Sulf antibody response in rabbits seems to be much more carrier-dependent when Sulf is coupled to heterologous serum protein compared to homologous (autologous) serum protein; 2) anti-NAD antibodies (antibodies directed against the new antigenic determinants introduced into the carrier through the coupling with hapten) were able to induce a secondary response to Sulf11RSA in rabbits primarily stimulated with Sulf10BGG; and 3) anti-NAD antibodies were able to induce an immune response to Sulf11RSA in rabbits made unresponsive to Sulf11RSA by i.v. injections of soluble Sulf11RSA. [ABSTRACT FROM AUTHOR]

The article presents information on the paper "Acute Vascular (Schonlein-Henoch) Purpura: An Immunologic Disease," by M.B. Kreidberg, W. Dameshek and R. Lortorraca. In this paper, fifteen cases of acute vascular purpura were investigated. Biopsies were carried out on 4 and in each case there was an acute inflammatory reaction involving the capillaries. The authors consider the fundamental lesions to be vasculitis and perivasculitis, and suggest that this may be caused by an antigen-antibody reaction in the small blood vessels.

The article presents information about meetings and symposiums that were held in year 1974 and 1975 for the study of various subjects related to human blood. The Fourteenth Annual Hanford Biology Symposium was held in Richland, Washington, in months of September and October of the year 1974. The Fourteenth Congress of the International Society of Blood Transfusion was held in July-August of the year 1975. The Ninth Congress of the World Federation was also arranged. Technical exhibitions were also held. Plenary sessions were held along with presentations which covered topics like: immune response, immunogenetics, optimal use of blood, haemostasis.

By using T cell-deprived mice and appropriate controls it has been shown that the adjuvant activity of LPS on the immune response to different doses of SRBC, tends to be oriented more towards B cells than towards T cells. In contrast, lentinan seems to mediate its adjuvant activity largely through a stimulatory effect on helper T cells. [ABSTRACT FROM AUTHOR]

The interaction between 7S IgG2 from unimmunized guinea-pigs and macrophage-rich peritoneal exudate cells from oil-stimulated guinea-pigs was examined by 125I-labelled IgG2 uptake. The cell uptake of 125I-labelled IgG2 reaches a maximum after 90 minutes at 20°; increased levels of labelling (1 to 23 atoms of iodine per immunoglobulin molecule) lead to slightly enhanced uptake, but the effect does not exceed experimental variability. Peripheral white blood cells bind relatively low levels of IgG2; the uptake by peritoneal cells is attributable primarily to a subpopulation of glass-adherent cells, presumably macrophages. Binding of IgG2 to macrophages is reversible even with a mild washing procedure. Repeated washing of cells did not affect the association constant, but the apparent number of receptor sites per cell was progressively reduced. After correction for the washing procedure employed, the number of IgG2 receptor sites was estimated as 2.5 ± 0.4 × 106 per cell; the association constant (Ka) was 1.46 ± 0.45 × 106 L/M at 20°. [ABSTRACT FROM AUTHOR]

The aim of the experiments was to find a T cell-mediated cytotoxic reaction where genetically determined low responsiveness is under the control of recessive genes. The T cell-mediated immune response to DBA/2 mastocytoma cells P 815-X2 in different inbred strains, F1 hybrids and congenic resistant strains of mice was determined using the 51Crk-release method. Two types of low responsiveness were found. The first already well documented type is characterized by dominance of low responsiveness in genetical analysis. It is due to tolerance because of the identity of the H-2 linked specificities of the recipient and of DBA/2 (H-2d) mice from which the turnout is derived. The second and new type of low responsiveness in T cell-mediated immunity was found in DBA/1 mice. In this strain low responsiveness is inherited as a recessive trait. The cytotoxic response of DBA/1J mice against the C57B1/6 lymphoma EL 4 is normal. Thus, their low responsiveness is restricted to a limited number of membrane determinants. [ABSTRACT FROM AUTHOR]

Chimaeric mice formed by manipulation of early embryos have been constructed between strains which differ in H-2 and immunoglobulin allotype. Cells forming antibodies to SRBC have been scored for allotype and H-2. The majority of the nine chimaeras analysed show no apparent gene transfer but this is not true for two mice. Possible interpretations of these results are discussed. [ABSTRACT FROM AUTHOR]

The primary in vitro response of cultured rabbit spleen cells to solubilized T2 phage (S-T2) was used to study the cellular requirements for immune in-induction. Rabbit lymph node cells, in contrast to spleen cells, were found not to respond to S-T2, and the addition of spleen cells insufficient in number to give rise to antibody in themselves failed to supply a missing cell type to lymph node cell cultures. The period in culture during which antibody formation by spleen cells could be induced was shown to be transitory, in that addition of S-T2 even 24 hours after culture initiation resulted in little, if any, antibody production. Cultures of non-adherent cells from spleen, obtained by removal of adherent cells on plastic dishes or glass bead columns, by silica treatment for removal of phagocytic cells, or by sequential treatment by adherence and with silica, responded as well to S-T2 as did the whole spleen cell population. These findings strongly indicate the relative macrophage independence of the in vitro response to S-T2 and are suggestive of the role of macrophages in solubilization of antigens, since intact phage fails to induce antibody formation in macrophage-deprived cultures. [ABSTRACT FROM AUTHOR]

Naturally occurring cellular and humoral immunity to a purified polyglycerophosphate (teichoic acid) have been observed in normal albino rats. Skin tests as well as in vitro correlates of delayed hypersensitivity yielded positive results in more than 50 per cent of rats between the ages of 24 and 40 weeks while rats 6-20 weeks old exhibited no cellular responses, Passive haemagglutination assays for natural antibodies to glycerol-teichoic acid revealed their occurrence in all rats between the ages of 6-20 weeks as well as in most of the older rats examined. These antibodies were usually found in the IgM fraction, but some animals possessed them in the IgG-containing fraction. The regular appearance of antibodies before the appearance of cellular response, if confirmed, may imply that B-cell responses precede T-cell responses in certain circumstances. [ABSTRACT FROM AUTHOR]

The induction in mice of a humoral immune response to intact sheep erythrocytes, both in vivo and in vitro, requires participation of thymus-derived (T) lymphocytes. In an in vitro system, spleen cells from both neonatally thymectomized and adult thymectomized irradiated bone marrow protected mice were successfully immunized, using washed sonicated sheep erythrocyte membrane fragments as antigen. This obviation of the requirement for T lymphocytes in the immune response, coupled with previous work on macrophage independence, indicates that sonicated membrane fragments were capable of directly immunizing bone marrow-derived (B) lymphocytes in vitro. These results further confirm the signal importance of antigenic structure in determining the cellular requirements for an immunological response; whereas antigens of particulate or monomeric form require the presence of both T cells and macrophages, polymeric antigens of intermediate size such as polymerized flagellin and sonicated sheep erythrocyte membranes require neither of these accessory cells. The results caution against the use of erythrocytes as models of thymus-dependent antigens. The data further suggest that reports of late antibody responses of relatively normal magnitude in thymectomized animals given larger doses of heterologous erythrocytes may have been due to direct immunization of B lymphocytes by degraded erythrocyte antigen. [ABSTRACT FROM AUTHOR]

Supernatants were obtained from cultures of keyhole limpet haemocyanin (KLH) primed mouse spleen cells, and also from cultures of KLH-educated, thymus-derived lymphocytes (T cells) after re-exposure of cells to the original priming antigen, KLH. These supernatants were able to facilitate the immune response of bone marrow-derived lymphocytes (B cells) to sheep erythrocytes (SRBC). Certain physical and biological properties of such supernatant activities are described. [ABSTRACT FROM AUTHOR]

HgA-positive red cells were treated in vitro with approximately 10 μmoles N-ethylmaleimide (NEM) per ml cells for 1 hour at 37° and then injected into the circulation of HgA-negative rabbits; all the cells were cleared within 24 hours After 1-3 months the animals were given a series of injections of untreated HgA-positive red cells at 3-monthly intervals. Five out of seventeen rabbits showed progressively diminishing survival of HgA-positive red cells with the development of anti-HgA. On the other hand, in eight rabbits red cell survival following three consecutive injections of untreated red cells was normal or almost normal and in four further rabbits survival was initially subnormal but became progressively longer and was almost normal following a third injection of cells. Thus, in as many as twelve out of seventeen animals (70 per cent) the survival of HgA-positive red cells following a third injection of untreated cells was normal or almost normal whereas this pattern was previously observed in only seven out of fifty-one animals (14 per cent) not given an initial injection of NEM-treated cells. It is concluded that the injection of NEM-treated HgA-positive red cells to HgA-negative rabbits induces a degree of immunological tolerance to the HgA antigen. [ABSTRACT FROM AUTHOR]

Long-term IgM and IgG responses to sheep red blood cells (SRBC) were determined in New Zealand Black (NZB) mice, using the plaque technique. As compared with other strains a prolonged spleen plaque-forming cell (PFC) response was found in young and old NZB mice. This phenomenon was found in the primary as well as in the secondary response and concerned IgM as well as IgG production. These observations are discussed in relation to the production of IgG antibodies of a low avidity. [ABSTRACT FROM AUTHOR]

Long persisting antigenic stimulation at immunogenic levels leads to a profound inhibition of antibody formation. With Brucellus abortus, there is first a brief and high IgM response. IgG antibody titres remain at a low level for some days, and then begin a slow and progressive increase, leading to a rather persistent maximum, and finally after about 300 days, to the state of inhibition. When the same total dose is given with monthly intervals, the effect is quite different, with similar IgM and IgG peaks being observed after each dose. The inhibited animals respond moderately to a ten-fold higher antigen dose, and only with IgG. Six months after interruption of the persistent antigenic stimulus, a strong response can be obtained after a new antigenic stimulation, with a substantial proportion of IgM. It is concluded that persistent antigenic stimulation plays a major role in the change from IgM to IgG synthesis. [ABSTRACT FROM AUTHOR]

The classes of immunoglobulin-containing cells in the lungs of mice after primary infection with Sendai virus were studied using an indirect immunofluorescence technique. It was found that during the first 5 days of the infection there was a considerable increase in all classes of immunoglobulin-containing cells with the IgA-containing cells retaining their pre-infection predominance. By the 6th day of the infection both IgG and IgA cells were present in equal numbers. This 1: 1 ratio persisted for nearly 30 days and was followed by a gradual reversion to IgA excess. IgM-containing cells represented only 1/15-1/30 of all immunoglobulin-containing cells at any time during the infection. [ABSTRACT FROM AUTHOR]

Injection of bovine serum albumin (BSA) with the capsular polysaccharide of Klebsiella pneumoniae (CPS-K) as adjuvant strongly primes mice for booster injections of BSA alone. The best doses of antigen for booster injections varied according to the frequency of antigen injections and the time interval between antigen injections. Increase in memory following the injection of BSA mixed with CPS-K adjuvant was first detected 10 days later. Memory continued to increase as the time interval after priming was increased to 90 days. Memory for the tertiary response increased after the optimum secondary antigenic stimulus. Increase in memory after the secondary antigenic stimulus was detected as early as 7 days after injection. Even secondary injection of the high dose of 50 mg of BSA did not exhaust immunological memory. Memory was also increased after the tertiary antigenic stimulus. Extremely high antibody responses (up to 492 mg protein per ml of antibody) could be obtained by eliciting tertiary and quaternary antibody responses optimally at the time memory was developed to the maximum level. [ABSTRACT FROM AUTHOR]

Plasmin digestion of rabbit IgG after pretreatment at low pH yields a fragment (Facb) which has lost the CH3 domain. A study of the biological activity of this fragment is described and the following conclusions are drawn: (1) Facb possesses the same antigen-combining capacity as the whole antibody; (2) Cl fixation is normal; (3) The capacity to sensitize target cells to lysis by cytotoxic K cells is lost; (4) Facb-antigen complexes are unable competitively to inhibit phagocytosis of sensitized bacteria by neutrophils. [ABSTRACT FROM AUTHOR]

Using the previously described animal model in which the effect of hepatic uptake of SRBC injected into the rat portal venous system was studied, the effect of two hepatotoxins carbon tetrachloride and D-galactosamine--is described. Carbon tetrachloride results in an enhanced primary immune response to SRBC injection and the abolition of the difference in immune response to repeated injections via the portal vein and inferior vena cava. Radioactive labelling of SRBC shows that the enhanced primary response is accompanied by a significant reduction of hepatic uptake. No significant increase in splenic uptake was noted. In contrast, the production of galactosamine hepatitis did not affect the immune response to SRBC. These findings are considered in the light of the pathogenesis of the hyperglobulinaemia which is associated with liver disease. [ABSTRACT FROM AUTHOR]

The role of Peyer's patches in primary and secondary immune response was studied with Vibrio cholerae as the antigen. V. cholerae E1 Tor ME 7 is a typical enteric antigen which was shown to be suitable for the demonstration of antibody forming cells by localized lysis in agar. No plaque-forming cells (PFC) against this antigen were found in the organs of non-immunized mice. Consequently a primary immune response could be studied. In vitro an immune response against this antigen could only be obtained with spleen cells when the donor animal had been primed. After primary intraperitoneal or enteral immunization many PFC were found in the spleen but none in Peyer's patches. this cannot be explained by insufficient penetration of the antigen into Peyer's patches as secondary responses were obtained with both routes of immunization. After local injection of antigen directly into Peyer's patches, PFC only appeared after 5 days. This is the indication that an essential cell type for the unable to restore the immune response in lethally irradiated mice, unless they were injected together with thymus cells or cells from peripheral lymph nodes. This suggests the absence of active T cells and indicates the presence of B cells in Peyer's patches. The combination of thymus cells and bone marrow cells was inactive in restoring the immune response. This is an indication that the B cells in Peyer's patches are immunologically more mature than bone marrow cells. [ABSTRACT FROM AUTHOR]

It was possible to demonstrate complement fixation by IgG1 and IgG3 sub-class myeloma proteins which had been heat aggregated under standard conditions. Phagocytosis of bacteria by neutrophils was inhibited by IgG 1, IgG2 and IgG3. Lysis of antibody-sensitized target cells by cytotoxic B lymphocytes was inhibited by all four sub-classes of IgG. IgG interacted with cytotoxic B lymphocytes, neutrophils and complement only after physical alteration. Cytotoxic B cell reacting activity was acquired during protein purification procedures and was only slightly increased by heating. Neutrophil inhibition activity appeared only after the IgG sub-classes were heated and aggregation had occurred. Very large aggregates, however, were inefficient inhibitory units. Complement fixation by IgG1 and IgG3 was markedly increased by heating and the largest aggregates showed greatest activity. [ABSTRACT FROM AUTHOR]

Production of antibody against major trasplantation antigens has been studied in sheep receiving osteoarticular allografts at the knee joint. These investigations have shown that this type of allograft leads to the rapid production of serum antibodies in the recipient animal. It was found that a high proportion of the sheep used in these studies possessed antibodies before operation. A large number of the animals which possessed antibody against major transplantation antigens prior to operation developed a wide spectrum of antibodies after operation more rapidly than did those recipients who had no pre-existing antibody. A smaller number showed an increase in antibody spectrum which was comparable with non-sensitized recipients. An analysis of the patters of antibody production was carried out in order to assess the possible benefits of reducing the bony component of the graft in lowering its immunogenicity. It was found that the thickness of bone carried by the graft was largely irrelevant and the immune response was initiated with only small amounts of bone. There is some evidence in this data that the surface area of bone is important in determining the pattern of the immune response. [ABSTRACT FROM AUTHOR]

Lymphocytes from seventeen cases of recent Mycoplasma pneumoniae infection, thirteen cases of previous infection and ten healthy subjects lacking antibodies to M. pneumoniae were cultured in the presence of various antigen preparations of M. pneumoniae. Lymphocyte stimulation was measured by the uptake of [14C]thymidine and by counting of morphologically transformed cells. The lymphocyte response to a sonicated concentrate of M. pneumoniae organisms and to a membrane fraction was significantly higher in recently infected patients than in healthy controls. However, nine out of ten serologically negative controls showed some degree of lymphocyte reactivity to M. pneumoniae. A lipid fraction of M. pneumoniae, which had a high antigen titre in the complement fixation test, induced no appreciable stimulation of lymphocytes from infected cases or control subjects. Lymphocyte responsiveness to sonicated M. pneumoniae antigen was demonstrable up to 10 years after infection. Among the cases with recent or previous M. pneumoniae infection there was no correlation between the degree of lymphocyte stimulation and the titres of antibodies to M. pneumoniae. [ABSTRACT FROM AUTHOR]

By the use of the leucocyte migration inhibition assay a cell-mediated immune response to Mycoplasma pneumoniae was demonstrated in seven out often patients examined 3-6 weeks after onset of lower respiratory-tract illness associated with M. pneumoniae infection. Six months after onset of illness M. pneumoniae-induced migration inhibition was only demonstrable in one out of four cases with a positive migration inhibition assay during the early period after infection. Among four other cases examined 1 year after infection inhibition of leucocyte migration was also demonstrable in only one case. The migration of leucocytes from eight healthy blood donors was not inhibited by M. pneumoniae antigen. Most cases examined by the migration inhibition assay were also examined for M. pneumoniae-induced lymphocyte stimulation in vitro. The lymphocyte stimulation test was more often positive than the migration inhibition assay. There was no quantitative correlation between these two tests. [ABSTRACT FROM AUTHOR]